Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany.
PLoS One. 2013 Sep 11;8(9):e73867. doi: 10.1371/journal.pone.0073867. eCollection 2013.
Although antimicrobial peptides protect mucus and mucosa from bacteria, Helicobacter pylori is able to colonize the gastric mucus. To clarify in which extend Helicobacter escapes the antimicrobial defense, we systematically assessed susceptibility and expression levels of different antimicrobial host factors in gastric mucosa with and without H. pylori infection.
We investigated the expression levels of HBD1 (gene name DEFB1), HBD2 (DEFB4A), HBD3 (DEFB103A), HBD4 (DEFB104A), LL37 (CAMP) and elafin (PI3) by real time PCR in gastric biopsy samples in a total of 20 controls versus 12 patients colonized with H. pylori. Immunostaining was performed for HBD2 and HBD3. We assessed antimicrobial susceptibility by flow cytometry, growth on blood agar, radial diffusion assay and electron microscopy.
H. pylori infection was associated with increased gastric levels of the inducible defensin HBD2 and of the antiprotease elafin, whereas the expression levels of the constitutive defensin HBD1, inducible HBD3 and LL37 remained unchanged. HBD4 was not expressed in significant levels in gastric mucosa. H. pylori strains were resistant to the defensins HBD1 as well as to elafin, and strain specific minimally susceptible to HBD2, whereas HBD3 and LL37 killed all H. pylori strains effectively. We demonstrated the binding of HBD2 and LL37 on the surface of H. pylori cells. Comparing the antibacterial activity of extracts from H. pylori negative and positive biopsies, we found only a minimal killing against H. pylori that was not increased by the induction of HBD2 in H. pylori positive samples.
These data support the hypothesis that gastric H. pylori evades the host defense shield to allow colonization.
尽管抗菌肽可以保护黏液和黏膜免受细菌侵害，但幽门螺杆菌仍能够在胃黏液中定植。为了明确幽门螺杆菌在多大程度上逃避了抗菌防御，我们系统地评估了有和无幽门螺杆菌感染的胃黏膜中不同抗菌宿主因子的易感性和表达水平。
我们通过实时 PCR 检测了 20 例对照和 12 例幽门螺杆菌定植患者的胃活检样本中 HBD1（基因名 DEFB1）、HBD2（DEFB4A）、HBD3（DEFB103A）、HBD4（DEFB104A）、LL37（CAMP）和 elafin（PI3）的表达水平。对 HBD2 和 HBD3 进行免疫染色。我们通过流式细胞术、血琼脂生长、放射状扩散测定和电子显微镜评估了抗菌敏感性。
幽门螺杆菌感染与诱导型防御素 HBD2 和抗蛋白酶 elafin 的胃内水平升高相关，而组成型防御素 HBD1、诱导型 HBD3 和 LL37 的表达水平保持不变。胃黏膜中 HBD4 的表达水平不显著。幽门螺杆菌株对防御素 HBD1 和 elafin 具有耐药性，对 HBD2 的耐药性呈菌株特异性，而 HBD3 和 LL37 则有效地杀死所有幽门螺杆菌株。我们证明了 HBD2 和 LL37 结合在幽门螺杆菌细胞表面。比较 H. pylori 阴性和阳性活检标本的抗菌活性，我们发现仅对 H. pylori 有最小的杀伤作用，而 HBD2 的诱导并没有增加这种杀伤作用。
这些数据支持了这样一种假设，即胃中的幽门螺杆菌逃避了宿主防御屏障以允许定植。
